Reference : Cross-regulation of cytokine signalling: Pro-inflammatory cytokines restrict IL-6 sig...
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/10993/16413
Cross-regulation of cytokine signalling: Pro-inflammatory cytokines restrict IL-6 signalling through receptor internalisation and degradation
English
Radtke, S. [Institute of Biochemistry, Medical School RWTH Aachen, 52074 Aachen, Germany]
Wüller, S. [Department of Paediatrics, Medical School RWTH Aachen, 52074 Aachen, Germany]
Yang, X.-P. [Institute of Biochemistry, Medical School RWTH Aachen, 52074 Aachen, Germany]
Lippok, B. E. [Institute of Biochemistry, Medical School RWTH Aachen, 52074 Aachen, Germany]
Mütze, B. [Institute of Biochemistry, Medical School RWTH Aachen, 52074 Aachen, Germany]
Mais, C. [Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, 97080 Würzburg, Germany]
Schmitz-Van De Leur, H. [Institute of Biochemistry, Medical School RWTH Aachen, 52074 Aachen, Germany]
Bode, J. G. [Department of Gastroenterology, Hepatology and Infectiology, Medical School Heinrich-Heine University, 40225 Düsseldorf, Germany]
Gaestel, M. [Department of Biochemistry, Medical School Hannover, 30625 Hannover, Germany]
Heinrich, P. C. [Institute of Biochemistry, Medical School RWTH Aachen, 52074 Aachen, Germany]
Behrmann, Iris mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) > Life Science Research Unit >]
Schaper, F. A [Department of Systems Biology, Otto-von-Guericke-University Magdeburg, Universitätsplatz 2, 38106 Magdeburg, Germany]
Hermanns, H. M. [Rudolf Virchow Center, DFG Research Center for Experimental Biomedicine, 97080 Würzburg, Germany]
2010
Journal of Cell Science
Company of Biologists
123
6
947-959
Yes (verified by ORBilu)
International
0021-9533
1477-9137
Cambridge
United Kingdom
[en] Crosstalk; Cytokine; Interleukin-6; Internalisation; Signalling
[en] The inflammatory response involves a complex interplay of different cytokines which act in an auto- or paracrine manner to induce the so-called acute phase response. Cytokines are known to crosstalk on multiple levels, for instance by regulating the mRNA stability of targeted cytokines through activation of the p38-MAPK pathway. In our study we discovered a new mechanism that answers the long-standing question how pro-inflammatory cytokines and environmental stress restrict immediate signalling of interleukin (IL)-6-type cytokines. We show that p38, activated by IL-1b, TNFa or environmental stress, impairs IL-6-induced JAK/STAT signalling through phosphorylation of the common cytokine receptor subunit gp130 and its subsequent internalisation and degradation. We identify MK2 as the kinase that phosphorylates serine 782 in the cytoplasmic part of gp130. Consequently, inhibition of p38 or MK2, deletion of MK2 or mutation of crucial amino acids within the MK2 target site or the di-leucine internalisation motif blocks receptor depletion and restores IL-6-dependent STAT activation as well as gene induction. Hence, a novel negative crosstalk mechanism for cytokine signalling is described, where cytokine receptor turnover is regulated in trans by pro-inflammatory cytokines and stress stimuli to coordinate the inflammatory response.
http://hdl.handle.net/10993/16413
10.1242/jcs.065326
http://www.scopus.com/inward/record.url?eid=2-s2.0-77951189931&partnerID=40&md5=3eea8c5e21b3e63dc516b64b24b29eaf
cited By (since 1996)19
Scopus

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